Abstract Background Regional level data on hospitalized heart failure (HHF) patients in Egypt is scarce. The aim of this study was to compare the demographics, clinical characteristics, and outcomes of HHF patients from four distinct geographical regions of Egypt. Results Study participants were part of the European Society of Cardiology Heart Failure Long Term (ESC-HF-LT) Registry, which enrolled patients from April 2011 to February 2014. A total of 1661 HHF patients from Egypt were enrolled, of whom 1645 were eligible for analysis: 914 from Alexandria, 249 from Cairo, 409 from the Delta region, and 73 from Upper Egypt. The mean age ranged from 52.2 to 62.8 years and differed significantly between the 4 groups (P < 0.01). Females represented one-third of the cohort (P = 0.5 between groups). The prevalence of obesity, diabetes, and hypertension also varied significantly across the groups (P < 0.01). The most common etiology of heart failure (HF) was ischemic heart disease. HF with reduced systolic function was the leading type of HF in the 4 groups (P = 0.6). The most common valvular abnormality in all regions was mitral regurgitation. For patients with prior history of HF, community-acquired infection was the most common reason for a HF exacerbation in all 4 groups. In-hospital mortality ranged from 2.9 to 7.7% in the 4 groups (P = 0.06). Only Alexandria and Delta groups provided reliable 1-year follow-up data, given low patient retention in Cairo and Upper Egypt groups. At one-year, 32% of patients from Alexandria compared to 22.6% from Delta were re-hospitalized for HF (P < 0.01). Mortality at 1 year was also significantly higher in Alexandria compared to Delta, 31.8 vs 13.2% respectively (P < 0.01). Conclusions HHF patients from different geographic regions of Egypt differed significantly in their demographics, clinical characteristics, and outcomes. Those differences underscore the importance of region-specific HF prevention and management strategies.